Cigarette smokers are studied in laboratory experiments designed to measure tobacco tolerance and dependence. Electrophysiologic, cardiovascular and subjective changes produced by inhaled tobacco smoke, in abstinent and non-abstinent smokers, are related to measures of puff volume and blood nicotine levels. The time course and symptoms of tobacco abstinence are measured in smokers hospitalized for two to three days to insure they do not smoke. Results to date indicate: (1) tolerance develops rapidly to many psychophysiologic changes produced by the first cigarette of the day; (2) consistent EEG and subjective changes occur during 12-to-18 hours of abstinence and are reversed by smoking; (3) smokers adjust the volume of smoke they inhale to compensate for differences in the nicotine yield of cigarettes, and (4) there is not a simple or direct relationship between a given smoker's pattern of smoking and blood nicotine levels.